cosmetics Article Investigation Utilizing the HLB Concept for the Development of Moisturizing Cream and Lotion: In-Vitro Characterization and Stability Evaluation Shoaib Alam 1, Mohammed S. Algahtani 2 , Mohammad Zaki Ahmad 2 and Javed Ahmad 2,* 1 Research & Development, Jamjoom Pharmaceuticals, Jeddah 21442, Saudi Arabia; [email protected] 2 Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 11001, Saudi Arabia; [email protected] (M.S.A.); [email protected] (M.Z.A.) * Correspondence: [email protected] or [email protected]; Tel.: +966-17542-8744 Received: 30 April 2020; Accepted: 30 May 2020; Published: 5 June 2020 Abstract: The current study aims to utilize the concept of the hydrophilic–lipophilic balance (HLB) value of ingredients for the development of a stable emulsion-based moisturizing cream and lotion for cosmetic application. The combination of a hydrophilic and lipophilic emulsifier such as glyceryl stearate (HLB value 3.8) and PEG-100 stearate (HLB value 18.8) were found to be effective to emulsify the chosen oil phase system at a specific concentration to achieve the required HLB for the development of the stable emulsion-based system. The developed formulation was characterized for pH, viscosity, spreadability, rheology, and droplet morphology. The influence of carbopol® ETD 2020 and the concentration of the oil phase on the rheology of the product was investigated and found to be significant to achieve the required thickening to convert the lotion into a cream. The formulation system developed through utilizing the concept of HLB was compared to a product developed through the conventional approach. It was observed that the utilization of the HLB method for the development of an emulsion-based product is a promising strategy compared to the conventional method. The physical stability and thermodynamic stability tests were carried out under different storage conditions. It was observed that the developed formulation was able to retain its integrity without showing any signs of instability during storage. Keywords: moisturizer; cream/lotion; cosmetics; HLB value; rheology; stabilit 1. Introduction The appearance of the skin and its function are well maintained by a significant balance between the water content and lipid content of the stratum corneum (SC) [1,2]. The balance can be disturbed by exposure to external stimuli such as humidity; ultraviolet radiation (UV); temperature; and endogenic factors, i.e., hormones [2,3]. Besides this, the regular application of soap; face wash; detergent; and topical irritants, including alcohol and hot water, can also strip lipids from the skin surface [2,4]. The disruption of this balance results in a dermatological condition known as dry skin, a condition observed mainly in patients with atopic dermatitis [2,5]. In these circumstances, suitable cosmetic products are used to improve skin hydration, preserve the skin’s natural condition, and avoid dryness of the skin. Moisturizers can improve skin dryness by maintaining water in the SC and creating an exogenous barrier to avoid transepidermal water loss (TEWL), which results in soft and moisturized skin [6,7]. Additionally, moisturizers help in treating skin dryness, ruggedness, and desquamation in non-treated psoriasis patients and in patients with acne who receive oral isotretinoin or topical tretinoin [6,8]. Moisturizers are also used to restore the skin barrier function in rosacea patients when used as an adjunctive therapy [9]. Cosmetics 2020, 7, 43; doi:10.3390/cosmetics7020043 www.mdpi.com/journal/cosmetics Cosmetics 2020, 7, 43 2 of 12 The hydration of the skin is restored by moisturizers through different mechanisms. For example, water from the aqueous phase may infiltrate the skin and contribute to an instant hydration effect. Additionally, humectants retain and attract large quantities of water to SC or the emollients from the lipid phase minimize the TEWL by filling the gaps between the desquamating corneocytes which helps to create smooth skin texture [6]. Additionally, emollients may interact with the intercellular skin lipids and restore the role of the skin as a barrier function and reduce the further loss of water. Emollient also shows occlusive properties to prevent water evaporation by creating a hydrophobic film over the skin [6]. Despite the important role of skin moisturizers to maintain the dignity and vitality of the skin to provide a healthy appearance, most of the available moisturizers are based on synthetic ingredients with known toxicity. Therefore, there is a considerable need to search for semi-synthetic/natural alternatives. In the vast majority, cosmetic preparations (lotion, cream, emulsion) are a biphasic semisolid formulation in which hydrophilic–lipophilic balance (HLB) plays a crucial role to balance the interfacial tension between the two immiscible liquids. A deep understanding of the HLB value helps to determine the required HLB (rHLB) which eventually helps to establish a stable biphasic emulsion formulation [10]. The HLB value permits the ability of the surfactant/emulsifier to stabilize the water-in-oil or oil-in-water emulsions. Surfactants with HLB values in the range of 4 to 8 usually stabilize water-in-oil emulsions (HLB number 4–6 results in the formation of poor emulsion; HLB number 6–8 results in the formation of a milky emulsion after vigorous agitation), while HLB values in the range of 8 to 18 stabilize oil-in-water emulsions (HLB number 8–10 results in the formation of a stable milky emulsion; HLB number 10–13 results in the formation of a translucent to clear emulsion; HLB number >13 results in the formation of a clear emulsion) [11]. The present investigation focuses on the formulation design of stable moisturizers, utilizing HLB concepts, their characterization, and the comparative evaluation of moisturizing cream with lotion. 2. Materials and Method 2.1. Materials Cetyl alcohol, disodium EDTA, glycerin, propylene glycol, mineral oil, and sodium hydroxide were obtained from Sigma-Aldrich (Taufkirchen, Germany). Alpha-Tocopherol was obtained from BASF Lampertheim (Lampertheim, Germany). Almond oil was obtained from Gustav Heess (Leonberg, Germany). The acrylic acid copolymer was obtained from Ashland Specialty Ingredients (Wilmington, DE, USA). Carbopol ETD 2020 was obtained from Lubrizol India Private Limited (Mumbai, India). Glyceryl stearate and PEG-100 stearate were obtained from Croda India (Mumbai, India). Dimethicone and dimethiconol were obtained from Dow Corning (Midland, MI, USA). Phenoxyethanol and ethylhexylglycerin were obtained from Salicylate and Chemical Private Limited (Mumbai, India). Aloe vera extract was obtained from Acetar Bio-Tech Inc (Xian, China). All the ingredients were of cosmetic/pharmaceutical grade. 2.2. Preparation of Moisturizing Cream and Lotion The emulsions were prepared following the design shown in Table1 by adopting the reported method with a slight modification [12,13]. The aqueous phase and the oil phase was prepared separately, as per the scheme shown in Table1. In a clean glass beaker, the required quantity of purified water was taken and heated up to 70 ◦C. Disodium EDTA was added into it under stirring until a clear solution was obtained. Carbopol ETD 2020 was added into a purified water solution under stirring until a lump-free dispersion was obtained. Glycerin, acrylic acid copolymer, propylene glycol, and Aloe vera extract were added into the aqueous dispersion system of carbopol under continuous stirring by maintaining the temperature of the aqueous phase to 70 ◦C. Similarly, for the preparation of the oil phase, mineral oil, glyceryl stearate, PEG-100 stearate, almond oil, and cetyl alcohol were taken into a clean glass beaker and heated all together up to 70 ◦C under continuous stirring until the clear phase was obtained. The aqueous phase and the oil phase were maintained at 70 ◦C with continuous Cosmetics 2020, 7, 43 3 of 12 stirring. The aqueous phase was poured into the oil phase under high-shear homogenization (using T 25 digital Ultra-Turrax, IKA-Werke, Staufen, Germany). The two phases were homogenized at 6500 rpm for 15 min at 70 ◦C and then cooled to room temperature. When the temperature of the developed emulsion system reached 50–55 ◦C, a post-emulsification material such as dimethicone, dimethiconol, alpha-tocopherol, phenoxyethanol and ethylhexylglycerin was added under continuous stirring and the mixture was cooled to room temperature. The initial pH of the developed moisturizing formulation was recorded and adjusted to a final pH of 5–6 with NaOH solution (1N). Table 1. Percentage composition of different formulations of moisturizing cream lotion. F1 F2 F3 F4 F5 Ingredients % w/w % w/w % w/w % w/w % w/w Aqueous Phase Material Disodium EDTA 0.025 0.025 0.025 0.025 0.025 Glycerin 8.000 3.000 3.000 3.000 3.000 Acrylic Acid - 2.000 - 2.000 2.000 Copolymer Propylene Glycol 0.500 0.500 - 1.000 1.000 Aloe vera extract 2.500 2.500 2.500 2.000 2.000 Carbopol ETD 2020 0.500 0.400 - 0.500 0.200 Oil Phase Material Mineral Oil 6.000 12.000 12.000 10.000 5.000 Glyceryl Stearate 3.000 2.500 1.500 4.986 2.493 PEG-100 Stearate 5.000 4.500 3.500 5.014 2.507 Almond Oil 2.000 2.000 3.000 2.000 1.000 Cetyl Alcohol 6.000 4.000 3.000 4.500 2.250 Post Emulsification Material Dimethicone 1.500 1.500 1.500 0.010 0.010 Dimethiconol 1.500 1.500 1.500 0.190 0.190 Alpha Tocopherol 0.100 0.100 0.100 0.500 0.500 Phenoxyethanol and 2.000 1.500 1.000 1.000 1.000 Ethylhexylglycerin Q.S to adjust Q.S to adjust Q.S to adjust Q.S to adjust Q.S to adjust Sodium Hydroxide pH 5.0–6.0 pH 5.0–6.0 pH 5.0–6.0 pH 5.0–6.0 pH 5.0–6.0 Purified Water Q.S to 100 Q.S to 100 Q.S to 100 Q.S to 100 Q.S to 100 2.3.